• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.709-717
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• 2017

Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of Escherichia coli heat-labile enterotoxin type IIa ($LT-IIa-B_5$), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to $LT-IIa-B_5$ were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that $LT-IIa-B_5$ enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by $LT-IIa-B_5$ serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.147-148
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• 2002

Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are encapsulated bacteria which encounter the respiratory mucosa and cause nasopharyngeal carriage that may lead to mild mucosal infections or severe invasive disease. (omitted)

• Molecules and Cells
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• v.22 no.2
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• pp.175-181
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• 2006

Delivery of DNA vaccines to airway mucosa would be an ideal method for mucosal immunization. However, there have been few reports of a suitable gene delivery system. In this study we used a cationic emulsion to immunize mice via the intranasal route with pCMV-S coding for Hepatitis B virus surface antigen (HBsAg). Complexing pCMV-S with a cationic emulsion dramatically enhanced HBsAg expression in both nasal tissue and lung, and was associated with increases in the levels of HBs-specific Abs in serum and mucosal fluids, of cytotoxic T lymphocytes (CTL) in the spleen and cervical and iliac lymph nodes, and of delayed-type hypersensitivity (DTH) against HBsAg. In contrast, very weak humoral and cellular immunities were observed following immunization with naked DNA. In support of these observations, a higher proliferative response of spleenocytes was detected in the group immunized with the emulsion/pCMV-S complex than in the group immunized with naked pCMV-S. These findings may facilitate development of an emulsion-mediated gene vaccination technique for use against intracellular pathogens that invade mucosal surfaces.

• Pediatric Infection and Vaccine
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• v.16 no.1
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• pp.13-23
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• 2009

Acute otitis media (AOM) and pneumonia are among the most common infectious diseases of children. Both are mucosal infections and share many common features such as etiological agents, pathogenesis and immunity. Influenza plays an important role in the pathogenesis of AOM and pneumonia. A vaccine against influenza may have substantial impact on these diseases during the influenza season. In clinical trials, influenza vaccine has reduced the incidence of AOM and pneumonia complicating influenza in children. However, the efficacy of vaccines has been controversial in children less than 2 years of age. Similarly, vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), both common causes of AOM and pneumonia, have the potential to reduce the impact of disease. Clinical trials showed that the currently licensed 7-valent pneumococcal conjugate vaccine (PCV), administered during infancy, had an efficacy of 6-7% for the prevention of AOM, however, visits to the clinic for AOM were reduced by up to 20-30% after routine use in the U.S. Both Hib and PCVs have a proven effectiveness of >20% for prevention of radiologically confirmed pneumonia in children. The recently introduced pnuemococcal vaccine conjugated with protein D is expected to reduce AOM and pneumonia caused by non-typable H. influenzae, in addition to its effects on pneumococcal diseases. Considering their high incidence in children, recent achievements in the prevention of AOM and pneumonia with vaccines may have a significant economic and social impact.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.735-745
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• 2024

Avian influenza is a serious threat to both public health and the poultry industry worldwide. This respiratory virus can be combated by eliciting robust immune responses at the site of infection through mucosal immunization. Recombinant probiotics, specifically lactic acid bacteria, are safe and effective carriers for mucosal vaccines. In this study, we engineered recombinant fusion protein by fusing the hemagglutinin 1 (HA1) subunit of the A/Aquatic bird/Korea/W81/2005 (H5N2) with the Bacillus subtilis poly γ-glutamic acid synthetase A (pgsA) at the surface of Lactobacillus casei (pgsA-HA1/L. casei). Using subcellular fractionation and flow cytometry we confirmed the surface localization of this fusion protein. Mucosal administration of pgsA-HA1/L. casei in mice resulted in significant levels of HA1-specific serum IgG, mucosal IgA and neutralizing antibodies against the H5N2 virus. Additionally, pgsA-HA1/L. casei-induced systemic and local cell-mediated immune responses specific to HA1, as evidenced by an increased number of IFN-γ and IL-4 secreting cells in the spleens and higher levels of IL-4 in the local lymphocyte supernatants. Finally, mice inoculated with pgsA-HA1/L. casei were protected against a 10LD50 dose of the homologous mouse-adapted H5N2 virus. These results suggest that mucosal immunization with L. casei displaying HA1 on its surface could be a potential strategy for developing a mucosal vaccine against other H5 subtype viruses.

• Journal of Plant Biotechnology
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• v.31 no.2
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• pp.151-161
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• 2004

Transgenic plants have been studied as delivery system for edible vaccine against various diseases. Edible plant vaccines have several potential advantages as follows: an inexpensive source of antigen, easy administration, reduced need for medical personnel, economical to mass produce and easy transport, heat-stable vaccine without refrigerator, generation of systemic and mucosal immunity and safe antigen without fetal animal-virus contaminants. The amount of recombinant antigens in transgenic plants ranged from 0.002 to 0.8％ in total soluble protein, depending on promoters for the expression of interested genes and plants to be used for transformation. Throughout the last decade, edible plant vaccine made notable progresses that protect from challenges against virus or bacteria. However edible plant vaccines have still problems that could be solved. First, the strong promoter or inducible promoter or strategy of protein targeting could be solved to improve the low expression of antigens in transgenic plants. Second, the transformation technique of target plant should be developed to be able to eat uncooked. Third, marker-free vector could be constructed to be more safety. In this review we describe advances of edible plant vaccines, focusing on the yields depending on plants/promoters employed and the results of animal/clinical trials, and consider further research for the development of a new plant-derived vaccine.

• IMMUNE NETWORK
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• v.4 no.3
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• pp.131-142
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• 2004

In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

• Journal of Oral Medicine and Pain
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• v.47 no.1
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• pp.62-66
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• 2022

Recent case studies raised the possibility that cutaneous and oral mucosal manifestations may be associated with the coronavirus disease 2019 (COVID-19) vaccination. A healthy 43-year-old male presented an acute aphthous stomatitis following Moderna COVID-19 vaccination. This rare case draws attention to a potential etiologic effect for oral mucosal manifestation from COVID-19 vaccination. Further investigation to shed light on prevalence and pathophysiologic association of this oral lesion and COVID-19 vaccination deserve attention.

• BMB Reports
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• v.31 no.5
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• pp.432-443
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• 1998

The poliovirus Sabin 1 strain has features that make it a particularly attractive live recombinant mucosal vaccine vehicle. Sabin 1 cDNA was manipulated to have multiple cloning sites and a viral specific 3C-protease cutting site at the N-terminal end of the polyprotein. The gene for the N-terminal 169 amino acids of the HIV-1 p24 was cloned into the multiple cloning site of the manipulated Sabin cDNA. A recombinant progeny virus was produced from HeLa cells when it was transfected with the RNA synthesized from the p24-Sabin chimeric cDNA. The recombinant progeny virus expresses substantial amounts of the HIV-1 p24 protein, which was clearly detected in the infected cell lysates and culture supernatants in Western blot experiments with rabbit anti-p24 serum and AIDS patients' sera. Differing from the Mahoney strain, the recombinant Sabin 1 poliovirus maintained the foreign gene stably during the subsequent passages. Replication capacity was about 1 to 1.5 log lower than that of the wild-type Sabin 1. Other physicochemical stability characteristics of the recombinant virus were similar to that of the wild-type Sabin 1. These results suggest that the manipulated Sabin 1 poliovirus can be used as a live viral vaccine vector for the development of mucosal vaccines.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.261-268
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• 2012

Respiratory syncytial virus (RSV) and influenza virus are the most significant pathogens causing respiratory tract diseases. Composite vaccines are useful in reducing the number of vaccination and confer protection against multiple infectious agents. In this study, we generated fusion of RSV G protein core fragment (amino acid residues 131 to 230) and influenza HA1 globular head domain (amino acid residues 62 to 284) as a dual vaccine candidate. This fusion protein, Gcf-HA1, was bacterially expressed, purified by metal resin affinity chromatography, and refolded in PBS. BALB/c mice were intranasally immunized with Gcf-HA1 in combination with a mucosal adjuvant, cholera toxin (CT). Both serum IgG and mucosal IgA responses specific to Gcf and HA1 were significantly increased in Gcf-HA1/CT-vaccinated mice. To determine the protective efficacy of Gcf-HA1/CT vaccine, immunized mice were challenged with RSV (A2 strain) or influenza virus (A/PR/8/34). Neither detectable viral replication nor pathology was observed in the lungs of the immune mice. These results demonstrate that immunity induced by intranasal Gcf-HA1/CT immunization confers complete protection against both RSV and homologous influenza virus infection, suggesting our Gcf-HA1 vaccine candidate could be further developed as a dual subunit vaccine against RSV and influenza virus.